A major effect of thyroid hormone is to promote growth and maturation. A small but crucial amount of thyroid hormone crosses the placenta, and the fetal thyroid axis becomes functional at midgestation. Thyroid hormone is extremely important for normal neurological development and proper bone formation in the fetus. In infants, insufficient fetal thyroid hormone causes congenital hypothyroidism, characterized by irreversible intellectual disability and short stature (see In the Clinic box).
Effects on Bone, Hard Tissue, and Dermis
Thyroid hormone promotes endochondral ossification, linear bone growth, and maturation of the epiphyseal bone centers. T3 enhances maturation and activity of chondrocytes in the cartilage growth plate, in part by increasing local growth factor production and action. During linear postnatal growth, T3 supports the actions of growth hormone, insulinlike growth factor (IGF)-I, and other growth factors. T3 also supports normal adult bone remodeling.
The progression of tooth development and eruption depends on thyroid hormone, as does the normal cycle of growth and maturation of the epidermis, its hair follicles, and nails. The normal degradative processes in these structural and integumentary tissues are stimulated by thyroid hormone. Thus either too much or too little thyroid hormone can lead to hair loss and abnormal nail formation. Thyroid hormone regulates the structure of subcutaneous tissue by inhibiting synthesis and increasing degradation of mucopolysaccharides (glycosaminoglycans) and fibronectin in the extracellular connective tissue (see later description of myxedema).
Effects on the Nervous System
Thyroid hormone regulates the timing and pace of development of the CNS. Thyroid hormone deficiency in utero and in early infancy inhibits growth of the cerebral and cerebellar cortex, proliferation of axons and branching of dendrites, synaptogenesis, myelination, and cell migration. Irreversible CNS impairment results when neonatal thyroid hormone deficiency is not recognized and treated promptly. These morphological defects are paralleled by biochemical abnormalities. Decreased thyroid hormone levels reduce cell size, RNA and protein content, tubulinand microtubuleassociated protein, protein and lipid content of myelin, local production of critical growth factors, and rates of protein synthesis.
Thyroid hormone also enhances wakefulness, alertness, responsiveness to various stimuli, auditory sense, awareness of hunger, memory, and learning capacity. In addition, normal emotional tone depends on proper thyroid hormone availability. Furthermore the speed and amplitude of peripheral nerve reflexes are increased by thyroid hormone, as is motility of the gastrointestinal tract.
In both women and men, thyroid hormone plays an important permissive role in regulation of reproductive function. The normal ovarian cycle of follicular development, maturation, and ovulation, the homologous testicular process of spermatogenesis, and maintenance of the healthy pregnant state are all disrupted by significant deviations in thyroid hormone levels from the normal range. In part these deleterious effects may be caused by alterations in the metabolism or availability of steroid hormones. For example, thyroid hormone stimulates hepatic synthesis and release of sex steroid–binding globulin.
Hypothyroidism referstoinsufficientproductionofthyroidhormonesandcanoccurasprimary,secondary,ortertiaryendocrinedisease(see ).Inprimaryhypothyroidism,T4andT3levelsareabnormallylowandTSHishigh.Insecondaryandtertiaryhypothyroidism,boththyroidhormonesandTSHarelow.TheresponseofTSHlevelstosyntheticTRHcanbeusedtodistinguishbetweenpituitaryandhypothalamicdisease.